JP2018066664A - Spectroscopic analyzer - Google Patents

Abstract

An analysis apparatus capable of performing spectroscopic analysis on a minute volume sample with high sensitivity is provided. A first branching portion and a second branching portion of an optical waveguide separate the probe light sent from the probe light source to the optical waveguide and mix them thereafter. At least one of the first branch part 11 and the second branch part 12 crosses the inside of the flow path 2 at the intersection 7 with the flow path 2. The excitation light source 3 irradiates the intersection 7 with excitation light. The light receiving unit 5 receives the probe light mixed after passing through the first and second branching units 11 and 12 and measures the light intensity thereof. [Selection] Figure 1

Description

  The present invention relates to a spectroscopic analyzer.

Conventionally, an absorptiometer is known as an analyzer for acquiring an absorption spectrum of a sample. The absorptiometer is based on the following Lambert-Beer law.
A = εcl = log (I ₀ / I)
here,
A: absorbance of sample ε: molar extinction coefficient c: concentration of sample l: optical path length I of light passing through sample I: transmitted light intensity I ₀ : incident light intensity.

  According to this, the absorbance of the sample is obtained from the ratio of the incident light intensity and the transmitted light intensity, but it can be seen that the sensitivity deteriorates as the optical path length becomes shorter.

  On the other hand, in recent years, a micro chemical chip using a micro space has been used for analyzing a micro sample. In such a micro space, since the optical path length is very short, when a conventional absorptiometer is used, the measurement sensitivity is greatly deteriorated. For example, if the optical path length in the conventional absorptiometer is 10 mm and the flow path width of the sample in the microchemical chip (that is, the optical path length) is 0.1 mm, the measurement sensitivity in the microchemical chip will be 1/100. . This makes it difficult to perform practical analysis.

  On the other hand, the present inventors have proposed a technique for irradiating a microfluid (that is, a sample) flowing through a microchannel with light and detecting the amount of heat generated by the sample as a phase change of the probe light (see Patent Document 1 below). . However, this technique has room for improvement in terms of measurement sensitivity because heat generated by light irradiation on the sample diffuses to the substrate.

  Moreover, in order to acquire a spectrum, it is necessary to use a white light source including multiple wavelengths. However, the power of the white light source is considerably lower than that of the laser. Therefore, when acquiring a spectral spectrum using the technique of the following patent document 1, some measures for obtaining sufficient measurement sensitivity may be required.

JP 2016-14630 A

  The present invention has been made based on the above situation. A main object of the present invention is to provide an analysis apparatus capable of performing spectroscopic analysis on a minute volume sample with high sensitivity.

  Means for solving the above-described problems can be described as follows.

(Item 1)
An optical waveguide, a flow path, an excitation light source, a probe light source, and a light receiving unit;
The optical waveguide includes a first branch portion and a second branch portion,
The first branch portion and the second branch portion are configured to separate the probe light sent from the probe light source into the optical waveguide and to mix the light thereafter.
At least one of the first branch part and the second branch part crosses the inside of the flow path at the intersection with the flow path,
The excitation light source is configured to irradiate the intersection with excitation light,
The light receiving section is configured to receive the probe light mixed after passing through the first and second branch sections and measure the light intensity thereof.

(Item 2)
It also has a substrate,
The spectroscopic analyzer according to item 1, wherein the optical waveguide and the flow path are formed inside or on an upper surface of the substrate.

(Item 3)
The spectroscopic analyzer according to item 1 or 2, wherein a width of the excitation light irradiated to the intersecting portion is substantially equal to a width of the flow path.

(Item 4)
An optical waveguide and a flow path;
The optical waveguide includes a first branch portion and a second branch portion,
The first branch part and the second branch part are configured to separate the probe light sent into the optical waveguide and to mix the probe light thereafter,
At least one of the first branch part and the second branch part crosses the inside of the flow path at the intersection with the flow path.

(Item 5)
A spectroscopic analysis method using the spectroscopic device according to item 4,
Flowing a sample through the flow path;
Sending probe light to the first branch portion and the second branch portion;
Irradiating the intersection with excitation light;
Receiving the probe light mixed after passing through the first and second branch parts and measuring the light intensity thereof.

  According to the present invention, it is possible to perform spectroscopic analysis on a sample with a small volume (for example, a sample flowing through a microchannel) with high sensitivity.

It is explanatory drawing for showing the schematic structure of the spectroscopic analyzer in one Embodiment of this invention. It is a top view which expands and shows the principal part of FIG. FIG. 3 is a schematic cross-sectional view taken along line AA in FIG. 2. In the drawing corresponding to FIG. 2, it is explanatory drawing for demonstrating the spot diameter of excitation light. It is explanatory drawing for demonstrating an example of the manufacturing method of the spectroscopy analyzer shown in FIG. 1, Comprising: It is a figure which shows the step which forms a flow path on a lower board | substrate. It is explanatory drawing for demonstrating an example of the manufacturing method of the spectroscopy analyzer shown in FIG. 1, Comprising: It is a figure which shows the step which forms a waveguide in a lower board | substrate. It is explanatory drawing for demonstrating an example of the manufacturing method of the spectroscopy analyzer shown in FIG. 1, Comprising: It is a figure which shows the step which laminates | stacks an upper board | substrate on the upper surface of a lower board | substrate. It is a graph which shows the result of the Example using the spectroscopic analyzer of this embodiment, Comprising: A horizontal axis shows time (second) and a vertical axis | shaft shows the magnitude | size (mV) of a photothermal conversion signal. It is a graph which shows the result of the Example using the spectroscopic analyzer of this embodiment, Comprising: A horizontal axis shows the density | concentration (micromol) of a sample, and a vertical axis | shaft shows the magnitude | size (mV) of a photothermal conversion signal.

  Hereinafter, a spectroscopic analyzer according to an embodiment of the present invention will be described with reference to the accompanying drawings.

(Configuration of this embodiment)
A spectroscopic analysis apparatus according to the present embodiment (hereinafter sometimes simply referred to as “analysis apparatus” or “apparatus”) includes an optical waveguide 1, a flow path 2, an excitation light source 3, a probe light source 4, and a light receiving unit. 5 as a main configuration (see FIG. 1). Furthermore, the apparatus of this embodiment includes a substrate 6 (see FIG. 1).

(Optical waveguide)
The optical waveguide 1 includes a first branch part 11 and a second branch part 12. The 1st branch part 11 and the 2nd branch part 12 become a structure which isolate | separates the probe light sent into the optical waveguide 1 from the probe light source 4, and mixes it after that. That is, the optical waveguide 1 constitutes a so-called Mach-Zehnder type waveguide.

  The first branch portion 11 crosses the inside of the flow path 2 at the intersection 7 with the flow path 2 (see FIGS. 2 and 3). Similarly, the second branch portion 12 of the present embodiment crosses the inside of the flow path 2 at a position away from the first branch portion 11. The optical waveguide 1 is made of a material having a higher refractive index than that of the substrate 6 (specifically, for example, glass having a high refractive index) inside the substrate 6. However, the first branching portion 11 and the second branching portion 12 in the present embodiment are configured by the flow channel 2 itself (or the sample itself that passes therethrough) at a portion that intersects the flow channel 2. . That is, the material (glass) constituting the optical waveguide 1 is separated so as to face each other with the flow path 2 interposed therebetween.

  In the present embodiment, the first branch portion 11 is disposed on the downstream side of the second branch portion 12 in the flow direction of the flow path 2. That is, the sample flow direction in the present embodiment is a right-to-left direction in FIG.

(Flow path)
The flow path 2 of this embodiment is for flowing a sample. The width of the flow path 2 of the present embodiment is, for example, 100 μm. However, the width of the flow path 2 is not limited to this, and can be, for example, about 1 μm to 1 mm. The depth of the flow path 2 is not particularly limited, but can be, for example, about 1 μm to 1 mm.

(Excitation light source)
The excitation light source 3 is configured to irradiate the intersection 7 with excitation light 31 (see FIG. 1). As the excitation light source 3, various white light sources such as a halogen lamp, a xenon lamp, and an LED can be used. However, if analysis for a plurality of wavelengths is not required, a monochromatic light source can be used as the excitation light source 3. Here, white means that a plurality of wavelengths necessary for obtaining a spectrum are included.

  The width (the so-called spot diameter) of the excitation light applied to the intersecting portion 7 is substantially equal to the width of the flow path 2 (see FIGS. 3 and 4). Specifically, the spot diameter d shown in FIG. 4 is about 107 μm in this example.

(Probe light source)
The probe light source 4 is for inputting probe light to the optical waveguide 1. As the probe light source, for example, a He—Ne laser and an optical fiber for transmitting laser light to the end of the optical waveguide 1 can be used. It is desirable that the probe light source 4 be capable of generating a wave whose phase is uniform enough to detect a phase change of the probe light described later.

(Light receiving section)
The light receiving unit 5 is configured to receive the probe light mixed after passing through the first and second branching units 11 and 12 and measure the light intensity thereof. The operation of the light receiving unit 5 in the present embodiment will be described later as an operation method of the present embodiment.

(substrate)
The optical waveguide 1 and the flow path 2 of the present embodiment are formed inside the substrate 6. In the present embodiment, the substrate 6 is composed of a lower substrate 61 and an upper substrate 62 laminated on the upper surface thereof. In the present embodiment, the upper substrate 61 and the lower substrate 62 are both made of glass that is transparent to excitation light. In the present embodiment, the lower substrate 61 and the upper substrate 62 are made of glass having a refractive index lower than that of the optical waveguide 1.

  In addition, the spectroscopic device provided with the optical waveguide 1 and the flow path 2 is configured by the configuration of the above-described embodiment.

(Operation method of this embodiment)
Next, the operation of the spectroscopic analyzer according to this embodiment will be described.

(Sample transfer)
First, a sample to be analyzed is fed from the end of the flow channel 2 (the lower end side in the example of FIG. 1) toward the inside of the flow channel 2. The sent sample flows through the flow path 2 in one direction. As a means for moving the sample in the flow path 2, for example, a pump can be used. Since the same method as the conventional method can be used for transferring the sample, further detailed description thereof will be omitted.

(Probe light input)
On the other hand, probe light is sent from the probe light source 4 into the optical waveguide 1. The probe light branches and proceeds to the first branching portion 11 and the second branching portion 12, and then joins again and is received by the light receiving portion 5. Here, in this embodiment, the glass which comprises the 1st branch part 11 and the 2nd branch part 12 shall not exist in the part which cross | intersects the flow path 2. However, since the width of the flow path 2 is narrow, the light passing through the flow path 2 is transmitted toward the light receiving unit 5 while maintaining a practically sufficient intensity.

(Excitation light irradiation)
In addition, excitation light is emitted from the excitation light source 3 toward the intersection 7 between the first branch portion 11 and the flow path 2. Then, the sample generates heat according to its light absorption characteristics, and the phase of the probe light passing through the first branching section 11 changes according to the amount of generated heat.

  The intensity of the interference light between the probe light passing through the first branching part 11 and the probe light passing through the second branching part 12 changes according to the phase change amount of the light passing through the first branching part 11. .

(Detection of phase change)
Thereafter, the light receiving unit 5 detects the intensity of the interference light. The light receiving unit 5 can detect the light absorption characteristics of the sample based on the detected intensity value of the interference light (or the corresponding phase change amount or heat generation amount).

  Here, according to the apparatus of the present embodiment, the wavelength of the light irradiated from the excitation light source 3 to the intersection 7 is changed by using a device such as a filter, a monochromator, or a prism, for example, so that the sample characteristics for each wavelength ( That is, a spectrum can be acquired.

  Moreover, in the apparatus of this embodiment, since the 1st branch part 11 has passed the inside of the flow path 2, the heat_generation | fever of the sample by irradiation of excitation light can be taken out efficiently as a wavelength change of probe light. There is an advantage that you can. If the first branching portion 11 is disposed outside the flow path 2, the heat generated in the flow path 2 diffuses in the three-dimensional direction, so that only a part thereof affects the change in wavelength of the probe light. Will give. That is, with such a technique, the measurement sensitivity of the sample tends to be low. On the other hand, in the apparatus of this embodiment, even if the heat generation of the sample diffuses in the three-dimensional direction, the probe light passes through the heat generating sample, so that the measurement sensitivity of the sample is improved. Can do. Then, in this embodiment, even when a low-power excitation light source such as a white light source is used, high measurement sensitivity can be obtained, and thus there is an advantage that a highly accurate spectral spectrum can be easily obtained.

  In the present embodiment, the width of the excitation light from the excitation light source 3 to the intersecting portion 7 (so-called spot diameter) is made substantially equal to the width of the flow path 2 (see FIGS. 3 and 4). If the width of the excitation light is wider than the width of the flow path 2, the excitation light heats the optical waveguide 1 outside the flow path 2. In general, the refractive index of glass increases by heating, and the refractive index of a sample decreases by heating. For this reason, if both the flow path 2 and the sample are heated, the change in the refractive index of the two cancels out, and the measurement accuracy may be lowered. On the other hand, according to the apparatus of this embodiment, the influence of such cancellation can be suppressed to a low level, and improvement in measurement accuracy can be expected.

  Furthermore, in the above-described embodiment, since the first branch portion 11 is arranged on the downstream side of the flow path 2 with respect to the second branch portion 12, the influence due to the temperature change of the sample passes through the second branch portion 12. Therefore, the measurement accuracy can be expected to be improved.

(Production method)
Next, an example of a method for manufacturing a spectroscopic device used in the spectroscopic analysis apparatus according to the present invention will be described with further reference to FIGS.

  First, the flow path 2 is formed by removing a part of the upper surface of the lower substrate 61 using, for example, wet etching using hydrofluoric acid (see FIG. 5).

  Subsequently, the optical waveguide 1 can be formed by irradiating the upper surface of the lower substrate 61 with, for example, the femtosecond pulse laser 8. This is because a portion having a high refractive index can be locally formed inside the glass by laser irradiation (FIG. 6).

  Next, the upper substrate 62 is bonded and bonded to the upper surface of the lower substrate 61. As this joining method, for example, a low temperature joining method can be used (FIG. 7).

(Example)
Next, the characteristics of the apparatus of the above-described embodiment were verified. The results are shown in FIGS. 8 and 9 as examples. In this example, an aqueous solution of sunset yellow (non-fluorescent dye) was used as a sample. The channel width was 100 μm.

  FIG. 8 shows the photothermal conversion signal (that is, the received light intensity measured by the light receiving unit 5) when the excitation light and the probe light are turned on / off, respectively. According to this, it can be seen that the received light intensity of the probe light changes due to the on / off of the excitation light.

  FIG. 9 shows the relationship between the sample concentration and the photothermal conversion signal. According to this, it can be seen that the sample concentration can be measured quantitatively using the measured value of the photothermal conversion signal.

  The contents of the present invention are not limited to the above embodiment. In the present invention, various modifications can be made to the specific configuration within the scope of the claims.

  For example, in the apparatus of the above-described embodiment, the second branch portion 12 intersects with the flow path 2, but the second branch portion 12 does not intersect with the flow path 2, and is above or below the flow path 2. It can also be configured to pass through.

  Furthermore, in the above-described embodiment, the first branch portion 11 is disposed on the downstream side of the flow channel 2 with respect to the second branch portion 12, but may instead be disposed on the upstream side of the flow channel 2. Is possible.

  Moreover, the 1st branch part 11 and the 2nd branch part 12 in above-described embodiment are only terms for distinguishing both relatively, and do not mean the restrictions beyond it. In short, the first branching section 11 and the second branching section 12 may be anything that can constitute a Mach-Zehnder type waveguide.

DESCRIPTION OF SYMBOLS 1 Optical waveguide 11 1st branch part 12 2nd branch part 2 Flow path 3 Excitation light source 4 Probe light source 5 Light receiving part 6 Substrate 61 Lower substrate 62 Upper substrate 7 Crossing part

Claims (5)

An optical waveguide, a flow path, an excitation light source, a probe light source, and a light receiving unit;
The optical waveguide includes a first branch portion and a second branch portion,
The first branch portion and the second branch portion are configured to separate the probe light sent from the probe light source into the optical waveguide and to mix the light thereafter.
At least one of the first branch part and the second branch part crosses the inside of the flow path at the intersection with the flow path,
The excitation light source is configured to irradiate the intersection with excitation light,
The light receiving section is configured to receive the probe light mixed after passing through the first and second branch sections and measure the light intensity thereof. It also has a substrate,
The spectroscopic analyzer according to claim 1, wherein the optical waveguide and the flow path are formed inside or on an upper surface of the substrate. The spectroscopic analyzer according to claim 1 or 2, wherein a width of the excitation light irradiated to the intersection is substantially equal to a width of the flow path. An optical waveguide and a flow path;
The optical waveguide includes a first branch portion and a second branch portion,
The first branch part and the second branch part are configured to separate the probe light sent into the optical waveguide and to mix the probe light thereafter,
At least one of the first branch part and the second branch part crosses the inside of the flow path at the intersection with the flow path. A spectroscopic analysis method using the spectroscopic device according to claim 4,
Flowing a sample through the flow path;
Sending probe light to the first branch portion and the second branch portion;
Irradiating the intersection with excitation light;
Receiving the probe light mixed after passing through the first and second branch parts and measuring the light intensity thereof.

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